BACKGROUND: Alloantibodies directed against the human neutrophil alloantigen (HNA)-3a are frequently implicated in severe and fatal transfusion-related acute lung injury (TRALI). The HNA-3a/3b system results from a single-nucleotide exchange (461G>A; Arg154Gln) in the choline transporter-like protein 2 gene. Genotyping may allow identification of blood donors at risk to develop HNA-3a antibodies. STUDY DESIGN AND METHODS: A polymerase chain reaction using sequence-specific primers (PCR-SSP) for genotyping of HNA-3a and -3b alleles was designed. Results of genotyping and phenotyping were compared in 40 randomly selected individuals and in blood donors and recipients of six TRALI cases associated with HNA-3a antibodies. Phenotyping was performed by granulocyte immunofluorescence and granulocyte agglutination using typing sera for HNA-3a and two recently found HNA-3b-reactive sera. Immunogenicity of HNA-3a was determined by the rate of HNA-3a alloantibodies in HNA-3b homozygous parous women. RESULTS: Genotyping and phenotyping results correlated to 100% and were in accordance with alloantibody formation and binding in HNA-3a antibody associated TRALI cases. Gene frequencies of HNA-3a and -3b were 0.792 and 0.207 in the German population with 64.1% homozygous individuals for the HNA-3a allele, 5.5% for the HNA-3b allele, and 30.4% heterozygous individuals, in accordance with the Hardy-Weinberg equilibrium and the gene frequencies of 0.819 and 0.181 reported in 1964. Immunization rates were estimated to be of 7% for HNA-3a and 0.5% for HNA-3b. CONCLUSION: The PCR-SSP method allows reliable determination of the HNA-3a and -3b genotypes; approximately 7% of HNA-3b homozygous women develop antibodies when exposed to the HNA-3a antigen during pregnancy.
BACKGROUND: Alloantibodies directed against the human neutrophil alloantigen (HNA)-3a are frequently implicated in severe and fatal transfusion-related acute lung injury (TRALI). The HNA-3a/3b system results from a single-nucleotide exchange (461G>A; Arg154Gln) in the choline transporter-like protein 2 gene. Genotyping may allow identification of blood donors at risk to develop HNA-3a antibodies. STUDY DESIGN AND METHODS: A polymerase chain reaction using sequence-specific primers (PCR-SSP) for genotyping of HNA-3a and -3b alleles was designed. Results of genotyping and phenotyping were compared in 40 randomly selected individuals and in blood donors and recipients of six TRALI cases associated with HNA-3a antibodies. Phenotyping was performed by granulocyte immunofluorescence and granulocyte agglutination using typing sera for HNA-3a and two recently found HNA-3b-reactive sera. Immunogenicity of HNA-3a was determined by the rate of HNA-3a alloantibodies in HNA-3b homozygous parous women. RESULTS: Genotyping and phenotyping results correlated to 100% and were in accordance with alloantibody formation and binding in HNA-3a antibody associated TRALI cases. Gene frequencies of HNA-3a and -3b were 0.792 and 0.207 in the German population with 64.1% homozygous individuals for the HNA-3a allele, 5.5% for the HNA-3b allele, and 30.4% heterozygous individuals, in accordance with the Hardy-Weinberg equilibrium and the gene frequencies of 0.819 and 0.181 reported in 1964. Immunization rates were estimated to be of 7% for HNA-3a and 0.5% for HNA-3b. CONCLUSION: The PCR-SSP method allows reliable determination of the HNA-3a and -3b genotypes; approximately 7% of HNA-3b homozygous women develop antibodies when exposed to the HNA-3a antigen during pregnancy.
Authors: Adam J Kanack; Julie A Peterson; Mia J Sullivan; Daniel W Bougie; Brian R Curtis; Richard H Aster Journal: Transfusion Date: 2011-10-27 Impact factor: 3.157
Authors: Ngoc D B Le; Gulen Yesilbag Tonga; Rubul Mout; Sung-Tae Kim; Marcos E Wille; Subinoy Rana; Karen A Dunphy; D Joseph Jerry; Mahdieh Yazdani; Rajesh Ramanathan; Caren M Rotello; Vincent M Rotello Journal: J Am Chem Soc Date: 2017-06-01 Impact factor: 15.419
Authors: Siti M Manaf; Hanis Z A NurWaliyuddin; Sundararajulu Panneerchelvam; Zainuddin Zafarina; Mohd N Norazmi; Geoffrey K Chambers; Hisham A Edinur Journal: Blood Transfus Date: 2015-04-20 Impact factor: 3.443
Authors: Nicole Schubert; Tom Berthold; Stefan Muschter; Jan Wesche; Birgitt Fürll; Angelika Reil; Jürgen Bux; Tamam Bakchoul; Andreas Greinacher Journal: Blood Transfus Date: 2013-07-11 Impact factor: 3.443